Investigation of effects of hyperlipidemia on IRE1α and insulin pathway in the cerebral cortex of ApoE-/- mice

AK, Deniz
Obesity prevalence increases worldwide. The most crucial reason for obesity is high-fat diet (HFD). Serum fatty acid levels are increased with HFD, inducing inflammation and glucose homeostasis disruption, leading to insulin signaling impairment linked to metabolic and neurodegenerative disorders in the brain. Glucose uptake of the cells is regulated by insulin through insulin receptor substrate (IRS) proteins, and disruption of this pathway results in insulin resistance. Hyperlipidemia, a lipid metabolism disorder associated with obesity, is the risk factor for neurodegenerative disorders. Therefore, it is crucial to elucidate the underlying cellular mechanisms of hyperlipidemia. Cellular stress and inflammatory response were accompanied by obesity. Although the stress origin has not been revealed yet, endoplasmic reticulum (ER) is linked with the stress response. The association between HFD and ER stress activation in rodents is well studied: moreover, ERS and insulin signaling impairment was substantially investigated in the hippocampus and frontal cortex of obese rats. In this study, the effects of high cholesterol diet along with HFD were examined on the activation of the IRE1α and insulin signaling pathway through the JNK/IRS/Akt pathway in the cortex of both C57BL/6 and ApoE-/- mice using Western blot analysis. Results indicated that there was not any statistically significant change in the insulin receptor-β (IR-β) expression in both groups. However, IRE1α/JNK/IRS-1/Akt pathway activation was increased in ApoE-/- mice with chow diet. Although IRE1α activation and stress status of the cells increased with impaired IRS-1 activation in ApoE-/- mice, there was no direct conclusion for the insulin signaling impairment.


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Citation Formats
D. AK, “Investigation of effects of hyperlipidemia on IRE1α and insulin pathway in the cerebral cortex of ApoE-/- mice,” M.S. - Master of Science, Middle East Technical University, 2022.